Gliederung

Objective

Cell replacement therapy, based on human fetal cell transplantation, proved to be beneficial under experimental conditions and in clinical trials. The ethical concerns and limited availability of the aborted tissue make it difficult for this therapy to become a routine clinical strategy. One way to overcome these obstacles is the in vitro expansion of human fetal-derived neural precursor cells, their characterization and differentiation into the desired phenotype for further clinical applications.

Results

All of the specimens expanded in vitro for more than 30 weeks with no signs of senescence. The majority of cells incorporated BrdU which was co-localized with both neuronal and glial markers. After differentiation precursors gave rise to neurons, astrocytes and oligodendrocytes. The expression of lineage specific markers was influenced by the origin of cultured tissue. The phylogenetically younger parts of the CNS (VM, SC) contained significant numbers of fully differentiated glial cells, whereas in cultures derived from telencephalon (CTX, STR) predominantly neurons with limited amounts of radial glia-like GFAP+ cells (CTX) or morphologically immature astrocytes (STR) were observed. The broad diversity of phenotype specific markers was detected in neurons from all cultured tissues with predominance of GAD+ cells (GABA-ergic neurons). Neurogranin- and ChAT- positive cells were more frequent in CTX and SC cultures but TH and serotonin reactivity was very limited.

Conclusions

The present study demonstrates the successful proliferation of human fetal-derived neural precursors and longterm differentiation into all cellular components of the CNS. The differentiation pattern was directly linked to the type of the tissue and age of the donor – resembling, in part, the ontogenetic maturation of the neuraxis. The in vitro proliferation of human fetal neural precursor cells might therefore be an alternative cell source for experimental and clinical research directed towards neural restorative strategies.